Autophagy Promotes Cigarette Smoke-Initiated and Elastin-Driven Bronchitis-Like Airway Inflammation in Mice.
Autophagy Promotes Cigarette Smoke-Initiated and Elastin-Driven Bronchitis-Like Airway Inflammation in Mice.
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自噬促进香烟烟雾引发和弹性蛋白驱动的小鼠支气管炎样气道炎症。
DOI：
10.3389/fimmu.2021.594330
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发表时间：
2021
影响因子：
7.3
通讯作者：
Chen ZH
中科院分区：
文献类型：
--
作者：
Huang HQ;Li N;Li DY;Jing D;Liu ZY;Xu XC;Chen HP;Dong LL;Zhang M;Ying SM;Li W;Shen HH;Li ZY;Chen ZH
香烟烟雾（CS）诱导的巨噬细胞激活和气道上皮损伤都是慢性阻塞性肺疾病（COPD）发展的关键，而自噬在这些过程中的最终功能仍然存在争议。我们最近开发了一种新的COPD小鼠模型，该模型基于CS致敏和弹性蛋白促进的自身免疫反应。因此，在本研究中，我们利用该模型来研究自噬在支气管炎样气道炎症发展的不同阶段中的作用。在COPD小鼠模型中，自噬标志物在气道上皮和肺组织中增加，Becn+/-或Lc3b-/ -小鼠表现出减少的中性粒细胞气道炎症和粘液分泌过多。此外，在cs致敏或弹性蛋白激发期间，自噬抑制剂3-甲基腺嘌呤（3-MA）均可显著抑制小鼠支气管炎样表型。短时间CS暴露可快速诱导肺泡巨噬细胞中基质金属肽酶12 （MMP12）的表达，而在CS暴露期间，多西环素（一种金属蛋白酶抑制剂）可有效减轻随之而来的弹性蛋白诱导的小鼠气道炎症。CS提取物在培养的巨噬细胞中触发MMP12表达，通过自噬损伤（Becn+/-或Lc3b-/ -）或抑制（3-MA或Spautin-1）减弱MMP12表达。综上所述，这些数据表明，自噬介导巨噬细胞中cs启动的MMP12激活和随后的气道上皮损伤，最终导致copd样气道炎症的发生。本研究再次强调抑制自噬是一种新的治疗cs诱导COPD的策略。
Cigarette smoke (CS)-induced macrophage activation and airway epithelial injury are both critical for the development of chronic obstructive pulmonary disease (COPD), while the eventual functions of autophagy in these processes remain controversial. We have recently developed a novel COPD mouse model which is based on the autoimmune response sensitized by CS and facilitated by elastin. In the current study, we therefore utilized this model to investigate the roles of autophagy in different stages of the development of bronchitis-like airway inflammation. Autophagic markers were increased in airway epithelium and lung tissues, and Becn+/- or Lc3b-/ - mice exhibited reduced neutrophilic airway inflammation and mucus hyperproduction in this COPD mouse model. Moreover, treatment of an autophagic inhibitor 3-methyladenine (3-MA) either during CS-initiated sensitization or during elastin provocation significantly inhibited the bronchitis-like phenotypes in mice. Short CS exposure rapidly induced expression of matrix metallopeptidase 12 (MMP12) in alveolar macrophages, and treatment of doxycycline, a pan metalloproteinase inhibitor, during CS exposure effectively attenuated the ensuing elastin-induced airway inflammation in mice. CS extract triggered MMP12 expression in cultured macrophages, which was attenuated by autophagy impairment (Becn+/- or Lc3b-/ -) or inhibition (3-MA or Spautin-1). These data, taken together, demonstrate that autophagy mediates both the CS-initiated MMP12 activation in macrophages and subsequent airway epithelial injury, eventually contributing to development COPD-like airway inflammation. This study reemphasizes that inhibition of autophagy as a novel therapeutic strategy for CS-induced COPD.
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DOI：
10.1056/nejmoa0904006
发表时间：
2009-12-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hunninghake GM;Cho MH;Tesfaigzi Y;Soto-Quiros ME;Avila L;Lasky-Su J;Stidley C;Melén E;Söderhäll C;Hallberg J;Kull I;Kere J;Svartengren M;Pershagen G;Wickman M;Lange C;Demeo DL;Hersh CP;Klanderman BJ;Raby BA;Sparrow D;Shapiro SD;Silverman EK;Litonjua AA;Weiss ST;Celedón JC
通讯作者：
Celedón JC
Beclin1 通过调节 USP10 和 USP13 的去泛素化活性来控制 p53 的水平。
影响因子：
64.5
作者：
Liu J;Xia H;Kim M;Xu L;Li Y;Zhang L;Cai Y;Norberg HV;Zhang T;Furuya T;Jin M;Zhu Z;Wang H;Yu J;Li Y;Hao Y;Choi A;Ke H;Ma D;Yuan J
通讯作者：
Yuan J
影响因子：
6.9
作者：
Houghton, A. McGarry
通讯作者：
Houghton, A. McGarry
自噬对于超细颗粒诱导的气道上皮炎症和粘液过度产生至关重要
影响因子：
13.3
作者：
Chen, Zhi-Hua;Wu, Yin-Fang;Shen, Hua-Hao
通讯作者：
Shen, Hua-Hao
DOI：
10.4049/jimmunol.1001603
发表时间：
2010-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Monick MM;Powers LS;Walters K;Lovan N;Zhang M;Gerke A;Hansdottir S;Hunninghake GW
通讯作者：
Hunninghake GW